Heart muscle damage is the final common pathway for most forms of cardiovascular disease and when extensive can impair quality of life and shorten survival. The most common cause is obstruction in coronary arteries, but the heart as well as other organs can be damaged by trauma, toxins, and infections. There are no currently approved therapies to generate new myocardium, or heart muscle. Stem cells have been administered intravenously (Hare et al. J Am Coll Cardiol. Dec. 8, 2009; 54(24):2277-2286), via infusion into the coronary arteries (Abdel-Latif et al. Arch Intern Med. May 28, 2007; 167(10):989-997, Johnston et al. Circulation. Sep. 22, 2009; 120(12):1075-1083) and by injection into the heart muscle itself (Williams et al. Circ Res. Apr. 1, 2011; 108(7):792-6). The results in terms of improved muscle function, however, have been very limited, possibly because of early “washout” (short duration of viable cells at the target site because of blood flow), the hostile environment into which the cells are delivered, and immunologic attack (Chavakis et al. Circulation; Jan. 19, 2010; 121(2):325-335, Terrovitis et al. Circ Res. Feb. 19, 2010; 106(3):479-494). Biomolecules released by the stem cells, called paracrine factors, may be responsible, in part, for their benefit (Gnecchi et al. Nat Med. April 2005; 11(4):367-368, Gencchi et al. Circ Res. Nov. 21, 2008; 103(11):1204-1219, Chimenti et al. Circ Res. Mar. 19, 2010; 106(5):971-980).
An embodiment relates to an implantable bioreactor comprising a housing comprising cells which produce paracrine factors in situ; wherein the housing comprises a barrier that shields the enclosed cells from immunological attack and permits the transfer of paracrine factors out of the housing. The implantable bioreactor can be for systemic or local delivery of paracrine factors. The implantable bioreactor housing can be in the form of a pouch, semi-permeable membrane, a cellular microenclosure or a matrix gel. The bioreactor can be optionally adhered to a medical device.
Another embodiment relates to a method for promoting healing of injured myocardium. The method comprises percutaneously delivering a bioreactor to the subject. The bioreactor comprises an enclosed housing and paracrine factor producing cells enclosed within the housing. The housing is impermeable to the paracrine factor producing cells, impermeable to immunological cells outside of the housing, and permeable to paracrine factors produced by the paracrine factor producing cells. The paracrine factors produced by the paracrine factor producing cells are released out of the housing to promote healing of the injured myocardium.
Another embodiment relates to a method for promoting healing of tissue in a subject. The method comprises delivering a bioreactor into a subject. The bioreactor comprises an enclosed housing and paracrine factor producing cells enclosed within the housing. The housing is impermeable to the paracrine factor producing cells, impermeable to immunological cells outside of the housing, and permeable to paracrine factors produced by the paracrine factor producing cells. The paracrine factors produced by the paracrine factor producing cells are released out of the housing to promote healing of the tissue.
Another embodiment relates to another method for promoting healing of tissue in a subject. The method comprises percutaneously delivering a bioreactor into the subject. The bioreactor is mounted on a catheter having at least one lumen and an infusion port. The at least one catheter lumen connects the infusion port with the housing lumen. The bioreactor comprises an enclosed housing having a lumen. The housing has pores of sufficient size to restrict the entry of immunological cells into the housing, restrict the egress of cells out of the housing, and allow the release of paracrine factors out of the housing. The method further includes introducing cells through the infusion port and into the housing lumen permitting the release of paracrine factors out of the housing to promote healing of the tissue.